|
|
Basic and Clinical Neuroscience، جلد ۱۲، شماره ۲، صفحات ۲۱۳-۲۲۲
|
|
|
| عنوان فارسی |
|
|
| چکیده فارسی مقاله |
|
|
| کلیدواژه‌های فارسی مقاله |
|
|
| عنوان انگلیسی |
Mutant Profilin1 Aggregation in Amyotrophic Lateral Sclerosis: An in Vivo Biochemical Analysis |
|
| چکیده انگلیسی مقاله |
Introduction: Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing mutant PFN1 may be a mechanism for motor neuron death. Hence, we were interested in investigating the aggregation of PFN1 further and searching for co-aggregated proteins in our mouse model overexpressing mutant PFN1. Methods: We investigated protein aggregation in several tissues of transgenic and no-transgenic mice using western blotting. To further understand the neurotoxicity of mutant PFN1, we conducted a pull-down assay using an insoluble fraction of spinal cord lysates from hPFN1G118V transgenic mice. For this assay, we expressed His6-tagged PFN1WT and PFN1G118V in E. coli and purified these proteins using the Ni-NTA column. Results: In this study, we demonstrated that mutant PFN1 forms aggregate in the brain and spinal cord of hPFN1G118V mice, while WT-PFN1 remains soluble. Among these tissues, spinal cord lysates were found to have PFN1 bands at higher molecular weights recognized with anti-PFN1. Moreover, the pull-down assay using His6-PFN1G118V showed that Myelin Binding Protein (MBP) was present in the insoluble fraction. Conclusion: Our analysis of PFN1 aggregation in vivo revealed further details of mutant PFN1 aggregation and its possible complex formation with other proteins, providing new insights into the ALS mechanism. |
|
| کلیدواژه‌های انگلیسی مقاله |
Motor neuron disease, Mutant PFN1 aggregation, Spinal cord, Transgenic mutant PFN1 mice |
|
| نویسندگان مقاله |
| Mina Nekouei
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
| Atousa Aliahmadi
Department of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
| Mahmoud Kiaei
Department of Pharmacology and Toxicology, Department of Neurology, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, USA.
| Ali Reza Ghassempour
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
|
|
| نشانی اینترنتی |
http://bcn.iums.ac.ir/browse.php?a_code=A-10-1631-1&slc_lang=en&sid=1 |
| فایل مقاله |
فایلی برای مقاله ذخیره نشده است |
| کد مقاله (doi) |
|
| زبان مقاله منتشر شده |
en |
| موضوعات مقاله منتشر شده |
Cellular and molecular Neuroscience |
| نوع مقاله منتشر شده |
Original |
|
|
|
برگشت به:
صفحه اول پایگاه |
نسخه مرتبط |
نشریه مرتبط |
فهرست نشریات
|